Plasmodium kinesin-8X associates with mitotic spindles and is essential for oocyst development during parasite proliferation and transmission


Autoři: Mohammad Zeeshan aff001;  Fiona Shilliday aff002;  Tianyang Liu aff002;  Steven Abel aff003;  Tobias Mourier aff004;  David J. P. Ferguson aff005;  Edward Rea aff001;  Rebecca R. Stanway aff007;  Magali Roques aff007;  Desiree Williams aff003;  Emilie Daniel aff001;  Declan Brady aff001;  Anthony J. Roberts aff002;  Anthony A. Holder aff008;  Arnab Pain aff004;  Karine G. Le Roch aff003;  Carolyn A. Moores aff002;  Rita Tewari aff001
Působiště autorů: School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, United Kingdom aff001;  Institute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck College, London, United Kingdom aff002;  Department of Molecular, Cell and Systems Biology, University of California Riverside, Riverside, California, United States of America aff003;  Biological Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal, Jeddah, Kingdom of Saudi Arabia aff004;  Nuffield Department of Clinical Laboratory Sciences, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom aff005;  Department of Biological and Medical Sciences, Faculty of Health and Life Science, Oxford Brookes University, Gipsy Lane, Oxford, United Kingdom aff006;  Institute of Cell Biology, University of Bern, Bern, Switzerland aff007;  Malaria Parasitology Laboratory, The Francis Crick Institute, London, United Kingdom aff008;  Research Center for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Kita-ku, Sapporo, Japan aff009
Vyšlo v časopise: Plasmodium kinesin-8X associates with mitotic spindles and is essential for oocyst development during parasite proliferation and transmission. PLoS Pathog 15(10): e1008048. doi:10.1371/journal.ppat.1008048
Kategorie: Research Article
doi: 10.1371/journal.ppat.1008048

Souhrn

Kinesin-8 proteins are microtubule motors that are often involved in regulation of mitotic spindle length and chromosome alignment. They move towards the plus ends of spindle microtubules and regulate the dynamics of these ends due, at least in some species, to their microtubule depolymerization activity. Plasmodium spp. exhibit an atypical endomitotic cell division in which chromosome condensation and spindle dynamics in the different proliferative stages are not well understood. Genome-wide shared orthology analysis of Plasmodium spp. revealed the presence of two kinesin-8 motor proteins, kinesin-8X and kinesin-8B. Here we studied the biochemical properties of kinesin-8X and its role in parasite proliferation. In vitro, kinesin-8X has motility and depolymerization activities like other kinesin-8 motors. To understand the role of Plasmodium kinesin-8X in cell division, we used fluorescence-tagging and live cell imaging to define its location, and gene targeting to analyse its function, during all proliferative stages of the rodent malaria parasite P. berghei life cycle. The results revealed a spatio-temporal involvement of kinesin-8X in spindle dynamics and an association with both mitotic and meiotic spindles and the putative microtubule organising centre (MTOC). Deletion of the kinesin-8X gene revealed a defect in oocyst development, confirmed by ultrastructural studies, suggesting that this protein is required for oocyst development and sporogony. Transcriptome analysis of Δkinesin-8X gametocytes revealed modulated expression of genes involved mainly in microtubule-based processes, chromosome organisation and the regulation of gene expression, supporting a role for kinesin-8X in cell division. Kinesin-8X is thus required for parasite proliferation within the mosquito and for transmission to the vertebrate host.

Klíčová slova:

Gametocytes – Kinesins – Motor proteins – Oocysts – Parasitic diseases – Plasmodium – Parasitic life cycles – Sporozoites


Zdroje

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